Reuters Health Information: Prucalopride safe and effective for men with chronic constipation

Prucalopride safe and effective for men with chronic constipation

Last Updated: 2015-05-18

By Larry Hand

NEW YORK (Reuters Health) - Already approved for use in
women, prucalopride is also safe and effective as a treatment
for chronic constipation in men, according to a new trial.

The drug, sold as Resolor by Shire, is a 5-hydroxytryptamine
receptor-4 agonist and acts by stimulating intestinal motility.
It is approved in Europe for treating chronic constipation in
women in whom laxatives fail to provide relief, based on
previous trials with mostly women participants.

"The evidence for effect is strong and equivalent to that of
the previous studies, which largely recruited female patients,
so I would expect this to be adequate to support (further)
approval," Dr. Yan Yiannakou from County Durham and Darlington
NHS Foundation Trust in Durham, UK, told Reuters Health by
email.

He and colleagues recruited men 18 and older with chronic
constipation for a trial involving 66 sites across Europe from
September 2010 to October 2013. They randomized participants to
receive prucalopride or placebo once a day. Patients younger
than 65 received 2 mg, while patients 65 or older received 1 mg,
with a possible boost to 2 mg.

Patients returned to treatment centers at weeks 2, 4, 8, and
12 for researchers to review daily electronic diary entries and
potential progress. Researchers asked the patients at weeks 4
and 12 to complete the Patient Assessment of
Constipation-Symptoms (PAC-SYM) questionnaire. They also
administered the Patient Assessment of Constipation-Quality of
Life (PAC-QOL) the same weeks.

Among 374 patients enrolled, more patients taking
prucalopride had a mean of three or more spontaneous complete
bowel movements (SCBMs) weekly (37.9% vs. 17.7%, p<0.0001), over
the 12-week treatment period.

At the final visit, 46.7% of prucalopride patients rated
their treatment as "quite a bit" or "extremely" effective,
compared with 30.4% of placebo patients (p<0.0001).

The proportion of patients who had improvement in the
PAC-QOL score came to 52.7% for the prucalopride group and 38.8%
for the placebo group (p=0.0035), the researchers report in the
American Journal of Gastroenterology, online April 14.

At baseline, 67.6% of patients in the prucalopride group and
56.2% of patients in the placebo group characterized their
constipation as severe or very severe. The corresponding
percentages at 12 weeks of treatment came to 21.9% for the
prucalopride group and 30.4% for the placebo group.

Seventy-eight (42.4%) of patients in the prucalopride group
and 64 (34.4%) of patients in the placebo group experienced at
least one treatment-emergent adverse event. Most were mild to
moderately severe. One patient experienced a severe event,
atrial fibrillation, in the prucalopride group, compared with
four patients in the placebo group (myocardial ischemia, lower
limb fracture, glottis carcinoma, and atelectasis). No deaths
occurred.

"On the basis of these findings, it can be concluded that
prucalopride once daily, taken for 12 weeks, is effective in the
treatment of chronic constipation in men. Both the efficacy and
safety results of this study were in line with observations in
the overall prucalopride population studied to date, which has
included predominantly female patients," the researchers write.

Dr. Yiannakou concluded, "There was no reason to expect the
results to be different in male patients so in that sense the
findings were not surprising."

Shire plc holds the rights to develop and market
prucalopride in the U.S., where it has not been approved. A
spokesperson for Shire did not respond to a request for comment
by deadline.

Shire has requested a label change from the European
Medicines agency based on the results of this trial. The company
issued the following statement through a spokesperson:

"Pending a positive final decision from EMA in the near
future on this submission, Shire plans to begin marketing
Resolor in Europe with an expanded indication for symptomatic
treatment of chronic constipation in adults in whom laxatives
fail to provide adequate relief. With respect to the U.S.,
prucalopride is in phase 3 development, and Shire has agreed
with (the Food and Drug Administration) on a regulatory path
forward for a (new drug application) submission. Should we
submit an NDA for prucalopride, we expect that we will include
the data from the phase 3 clinical study in men. We continue to
work towards meeting the requirements agreed between Shire and
FDA and have not yet disclosed timing for a potential NDA
submission."

Shire-Movetis NV funded this study and employed two
coauthors at the time of the study. Dr. Yiannakou and two
co-authors have reported financial ties to the company.